The Prostate 66:157 ^172 (2006) Cytogenetic and Expression Profiles Associated WithTransformation to Androgen-Resistant Prostate Cancer See-Tong Pang, 1,2 * Wen-Hui Weng, 2 Amilcar Flores-Morales, 2 Bjo ¨ rn Johansson, 3 Mohammad R. Pourian, 3 Peter Nilsson, 4 A ˚ ke Pousette, 3 Catharina Larsson, 2 and Gunnar Norstedt 2 1 Department of Surgery, Division of Urology,Chang Gung Memorial Hospital,TaoYuan,Taiwan 2 Department of Molecular Medicine, Karolinska Hospital, Karolinska Institutet, Stockholm, Sweden 3 Department of Woman and Child Health, Andrology Center, Karolinska Hospital, Karolinska Institutet, Stockholm, Sweden 4 Department of Biotechnology, KTH^Royal Institute of Technology, AlbaNova University Center, Stockholm, Sweden BACKGROUND. The mechanisms underlying the progression of prostate cancer to androgen- resistant cancer are still not fully understood. Here, we studied the genetic events associated with this transformation. METHODS. The androgen sensitive prostate cancer cells line LNCaP-FGC and its androgen resistant subline LNCaP-r were investigated using SKY, CGH, and cDNA microarray. RESULTS. Karyotypically, several additional chromosomal aberrations were seen in LNCaP-r as compared to the parental line. CGH also revealed unique net chromosomal alterations in LNCaP-r compared to LNCaP-FGC, including gain of 2p13-23, 2q21-32, and 13q and loss of 6p22-pter. cDNA microarray analysis identified several genes involved in DNA methylation, such as DNMT2, DNMT3a, and methyl-CpG binding domain protein 2 and 4 that were higher expressed in LNCaP-r. Interestingly, androgen responsiveness of LNCaP-r was restored after treated with DNA methyltransferase inhibitor. CONCLUSIONS. Our findings may serve as a basis for molecular dissection of the mechanisms involved in development of androgen resistant prostate cancer. Prostate 66: 157–172, 2006. Published 2005 Wiley-Liss, Inc. { KEY WORDS: prostate cancer; androgen resistance; DNA microarray; spectral karyo- type; CGH INTRODUCTION Prostate cancer is the leading cancer among men in the industrialized Western countries [1]. In the United States, it has been estimated that every sixth man will be diagnosed with prostate cancer during his lifetime [2]. Nevertheless, the molecular mechanisms for prostate cancer development and progression still remain largely unknown [3]. Prostate cancer is a heterogeneous disease with clinical phenotypes of varying aggres- siveness. Organ-confined prostate cancer can be cured with radical prostatectomy, whereas for patients with advanced tumors the prognosis is generally poor. See-Tong Pang and Wen-Hui Weng contributed equally to this work. Grant sponsor: Swedish Society for Medical Research; Grant number: A200300843; Grant sponsor: Swedish Medical Research Council; Grant number: VR13X-08556; Grant sponsor: Swedish Cancer Society; Grant sponsor: Knut and Alice Wallenberg Founda- tion; Grant number: KAW 2003.0043; Grant sponsor: Stockholm County Council; Grant sponsor: Chang Gung Memorial Hospital, Taiwan. *Correspondence to: Dr. See-Tong Pang, Department of Surgery, Division of Urology, Chang Gung Memorial Hospital, No.5 Fushing Street, Kwei-Shan, 333 Tao-Yuan, Taiwan. E-mail: jacobpang@cgmh.org.tw Received 16 May 2005; Accepted 28 June 2005 DOI 10.1002/pros.20328 Published online 19 September 2005 in Wiley InterScience (www.interscience.wiley.com). ß 2005 Wiley-Liss, Inc.